Báo cáo y học: "Cough: are children really different to adults" pot

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Cough
Open Access
Review
Cough: are children really different to adults?
Anne B Chang*
Address: Paediatric Respiratory and Sleep Physician, NHMRC Practitioner Fellow, Associate Professor in Paediatrics and Child Health, Dept of
Respiratory Medicine, Royal Children's Hospital, Herston Rd, Brisbane, Queensland 4029, Australia
Email: Anne B Chang* -
* Corresponding author
Abstract
Worldwide paediatricians advocate that children should be managed differently from adults. In this
article, similarities and differences between children and adults related to cough are presented.
Physiologically, the cough pathway is closely linked to the control of breathing (the central
respiratory pattern generator). As respiratory control and associated reflexes undergo a
maturation process, it is expected that the cough would likewise undergo developmental stages as
well. Clinically, the 'big three' causes of chronic cough in adults (asthma, post-nasal drip and
gastroesophageal reflux) are far less common causes of chronic cough in children. This has been
repeatedly shown by different groups in both clinical and epidemiological studies. Therapeutically,
some medications used empirically for cough in adults have little role in paediatrics. For example,
anti-histamines (in particular H
1
antagonists) recommended as a front-line empirical treatment of
chronic cough in adults have no effect in paediatric cough. Instead it is associated with adverse
reactions and toxicity. Similarly, codeine and its derivatives used widely for cough in adults are not
efficacious in children and are contraindicated in young children. Corticosteroids, the other front-
line empirical therapy recommended for adults, are also minimally (if at all) efficacious for treating
non-specific cough in children. In summary, current data support that management guidelines for
paediatric cough should be different to those in adults as the aetiological factors and treatment in

children significantly differ to those in adults.
Introduction
To health care professionals who work with them, chil-
dren are clearly different to adults but this seems less obvi-
ous to some. "Children swallow just like adults",
remarked an academic speech pathologist when com-
menting on dysphagia and cough. "Children are the same
as adults. It's just the behaviour that is different",
remarked another specialist. Paediatricians world-wide
passionately advocate that childhood illnesses should be
managed differently to adults as extrapolation of adult
based data to children can result in unfavourable conse-
quences [1,2]. This article provides an update on paediat-
ric issues on cough and highlights the differences between
adults and children that are relevant to cough.
Physiology
Central and peripheral cough pathway
The central pathway for cough is a brainstem reflex linked
to control of breathing (the central respiratory pattern
generator) [3], which undergoes a maturation process
such that the reference values for normal respiratory rate
in children are different to those in adults [4] and reaches
adult values in adolescence. In early life, cough is related
to primitive reflexes (laryngeal chemoreflex), that
Published: 20 September 2005
Cough 2005, 1:7 doi:10.1186/1745-9974-1-7
Received: 06 July 2005
Accepted: 20 September 2005
This article is available from: />© 2005 Chang; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( />),

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cough 2005, 1:7 />Page 2 of 15
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undergo maturation resulting in significant differences in
swallowing between young children and adults [5]. Plas-
ticity (modulation) of the cough reflex has been shown
[3,6], although it is unknown if the young have greater
plasticity (propensity to modulate or change). Like other
organs directly relevant to cough (eg the systemic and
mucosal immune system) [7,8] or not directly related to
cough (eg the renal system), one can speculate that the
cough reflex has maturational differences as well. Indeed
children differ from adults in some immunological
response to lipopolysaccharides [9]. Also, children, espe-
cially their neurological system, are more sensitive than
adults to certain environmental exposures [10]. For exam-
ple, in children, the utility of CT scans has to be balanced
with the reported increased lifetime cancer mortality risk,
which is age and dose dependent. Although the risk is rel-
atively negligible, children have 10 times increased risk
compared to middle aged adults [10]. Lastly, the distinct
differences in respiratory physiology and neuro-physiol-
ogy between young children and adults include matura-
tional differences in airway, respiratory muscle and chest
wall structure, sleep characteristics, respiratory reflexes
and respiratory control [11-13].
Cortical control of cough and psychological determinants
Cough can be cortically modulated [14]. In adults,
chronic cough is associated with anxiety as an independ-
ent factor [15]; such data are unavailable in children.

Adults seeking medical attention are primarily self-driven
but in children, parental and professional expectations
influence consulting rates and prescription of medica-
tions [16-18]. Reporting of childhood respiratory symp-
toms is biased and parental perception of childhood
cough plays an important role [19,20]. In asthma, paren-
tal psychosocial factors (in particular anxiety) were
strongest predictors for emergency attendances for chil-
dren whereas in adults, asthma severity factors were the
risk factors [21]. In cough, use of cough medications and
presentation to doctors were less likely in children with
higher educated mothers [22]. Hutton and colleagues'
described "parents who wanted medicine at the initial
visit reported more improvement at follow-up, regardless
of whether the child received drug, placebo, or no treat-
ment" [23]. Rietveld and colleagues showed that children
were more likely to cough under certain psychological set-
tings [24,25].
Clinical evaluation of cough
What is 'normal' or expected?
'Normal' children occasionally cough as described by two
studies that objectively measured cough frequency
[26,27]. Normal children without a preceding upper res-
piratory infection in the last 4 weeks have up to 34 cough
epochs per 24 hours [26]. In another study, 0–141 cough
epochs/24 hours (median 10) were recorded in 'controls'
(these children were considered well by parents and
attending school and were age, gender and season
matched [27]). Medicalisation of an otherwise common
symptom can foster exaggerated anxiety about perceived

disease and lead to unnecessary medical products and
service [28]. Cough in this situation is termed 'expected
cough'. Such data are unavailable in adults.
However, concerns of parents presenting to general prac-
titioners for their children's cough can be extreme (fear of
child dying, chest damage) [29,30]. Other parental con-
cerns were disturbed sleep and relief of discomfort [29].
However the burden of illness on children and their fam-
ily has not been well described. In contrast adult data have
shown that chronic cough causes a significant burden of
illness (physical and psychosocial) that is often not appre-
ciated by physicians [20] as reflected in adult cough-QOL
scores [31,32].
What is acute and what is chronic?
The utility of definitions depends on the intention of use.
In adults, chronic cough is defined as cough lasting >8
weeks [33]. In children the definition of chronic cough
varies from 3-weeks duration [34] to 12-weeks [35,36].
There are no studies that have clearly defined when cough
should be defined chronic or persistent. As studies have
shown that cough related to ARIs resolves within 1 to 3
weeks in most children [17,37] it would be logical to
define chronic cough as daily cough lasting >4 weeks.
Classification of types of cough in children (reproduced from [110])Figure 1
Classification of types of cough in children (reproduced from
[110]).
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Classification of paediatric cough
Paediatric cough can be classified in several ways, based

on aetiology [38], timeframe [35] and characteristic
(moist vs dry). For practical reasons, guidelines based on
cough duration, combined with cough quality have been
developed [35]. An evidence based guideline specific for
paediatrics will be published as part of the American Col-
lege of Chest Physicians' Guidelines on the Management
of Cough in Adults and Children [39]. The previous
guidelines which stated that "the approach to managing
cough in children is similar to the approach in adults"
[34] was arguably inaccurate.
Unlike cough in adults, paediatric cough has also been
classified into specific and non-specific cough (with an
overlap) for practical reasons (figure 1). Indeed, the most
common paradigm encountered in clinical paediatrics
when cough is a presenting feature is the differentiation
between specific and non-specific cough. Specific cough
refers to cough in the presence of pointers (table 1) that
suggest the presence of an underlying aetiology. A thor-
ough history and examination to elucidate these points
are necessary when assessing children with cough and in
the majority of situations, specific cough aetiologies can
be defined. While some of these symptoms and signs are
common in adults (such as haemoptysis), others are not
(such as failure to thrive). Unlike in adults, where cough
characteristics has been shown to be of little diagnostic
value [40], paediatricians often recognise certain cough
qualities such as staccato cough (table 2). A chronic moist
cough is always abnormal and represents excessive airway
secretions [41]. However in a small group of children nat-
ural resolution may occur [42] and a specific paediatric

diagnostic category may not be found [43]. A chronic dry
cough however may represent a dry phase of an otherwise
usually moist cough or airway secretions too little to influ-
ence the cough quality [41]. Chronic dry cough in the
absence of specific pointers (table 1) in the history and
examination is termed 'non-specific cough' or 'isolated
cough', ie cough is the sole symptom. In non-specific
cough, the aetiology is ill defined and we suspect that the
majority are related to post viral cough and/or increased
cough receptor sensitivity [44,45]. However in the major-
ity of children, it is most likely related to a non serious
aetiology [38] or may spontaneously resolve as evidenced
in the placebo arms of RCTs [46-48] and cohort studies
[49-51]. Thus if one assumes that the natural resolution of
non-specific cough occurs in 50% of children, 85 children
per study arm is required in a randomised controlled trial
to detect a 50% difference between active and placebo
groups, for a study powered at 90% at the 5% significance
level.
Symptoms
Nocturnal cough
In both adults and children, a major problem in utilising
the symptom of nocturnal cough is the unreliability and
inconsistency of its reporting when compared to objective
measurements [52-54]. In children, however, two groups
have reported that parents were able to detect change
[46,54], albeit only moderately well. The ability to detect
cough change was better in children with a history of trou-
blesome recurrent cough (r = 0.52) than in children with-
out (r = 0.38) [54]. Relationship between change in cough

frequency and change in subjective scores has not been
examined in adults.
Nocturnal cough is often used as a hallmark of asthma as
children with asthma often report troublesome nocturnal
cough [55]. However in a community based study, only a
third of children with isolated nocturnal cough had an
asthma-like illness [56]. To date there are no studies that
have objectively documented that nocturnal cough is
worse than daytime cough in children with unstable
asthma. One study showed that cough frequency was
higher during the day than at night in a group of children
with stable asthma who were on ICS yet had elevated lev-
els of eNO but not sputum eosinophils [57] (arguably the
best marker for eosinophilic inflammation in stable
asthma [58]) in schoolchildren. Whether the increased
eNO is a marker of asthma instability or related to other
causes of elevated nitric oxide (such as environmental
pollutants) [59,60] is unknown. Nocturnal cough has
been reviewed elsewhere [61].
Cough quality
Unlike adults, cough quality is associated with specific
aetiology in children (table 2). Except for brassy cough
and wet cough, the sensitivity and specificity of cough
quality have not been defined [62]. Thus perceived cough
quality by parents and clinicians may have limitations.
Table 1: Pointers to underlying aetiology i.e. presence of specific
cough [39,110]
auscultatory findings
cough characteristics eg cough with choking, cough quality (table 2),
cough starting from birth

cardiac abnormalities (including murmurs)
chest pain
chest wall deformity
chronic dyspnoea
daily moist or productive cough
digital clubbing
exertional dyspnoea
failure to thrive
feeding difficulties
haemoptysis
immune deficiency
neurodevelopmental abnormality
recurrent pneumonia
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Pertussis-like cough in children may indeed be caused by
adenovirus, parainfluenza viruses, respiratory syncytial
virus and Mycoplasma [63]. Children with a dry cough are
more likely to naturally resolve than those with wet cough
[64]. Young children rarely expectorate even when airway
secretions are excessive. Hence wet/moist cough is often
used interchangeably with productive cough [65,66] a
term used in adults. We have recently shown the clinical
validity of dry and wet/moist cough in children by scoring
secretions seen during bronchoscopy [41]. In contrast,
quality of cough has been shown to be of little use in
adults [40,67].
Investigations
Children with specific cough usually require a variety of
investigations which include chest CT, bronchoscopy,

barium meal, video fluoroscopy, nuclear scans, sweat test,
etc. The role of these tests for evaluation of lung disease is
beyond the scope of this article as it would encompass the
entire spectrum of paediatric respiratory illness. The more
common problem of non-specific cough is further briefly
discussed. In general investigations are rarely needed in
non-specific cough.
Airway cellular assessment
Examination of cellular profile of induced sputum, a
standard in some adult cough clinics, can only be per-
formed in older children (children >6 years). The majority
of children with chronic cough seen by paediatricians are
in the toddler age group (1–5 years) where bronchoscopy
is necessary to obtain airway cells. In contrast to adult
studies, all 4 paediatric studies [51,68-70] that have exam-
ined airway cellularity in children with chronic cough
have rarely found an asthma-like profile. Other than
assessment of airway specimens for microbiological
purposes, the use of airway cellular and inflammatory
profile in children with chronic cough is currently entirely
limited to supportive diagnosis and research rather than
definitive diagnosis. This is in contrast to that in adults
with chronic cough where some have suggested use of air-
way inflammatory profiles to direct therapy [71,72]. One
study in children with 'cough variant asthma' (mean age
11 years) showed that those with a higher percentage
(>2.5%) of eosinophils in their sputum were more likely
to develop classical asthma on follow-up [73]. There was
however no appropriate control group and sputum ECP
was unpredictive of asthma [73].

Cough sensitivity measures
In the physiology of cough, gender differences in CRS well
recognised in adults [74], are absent in children [44]. In
children, CRS is instead influenced by airway calibre and
age [44]. An adult type approach to CRS measurement
that is reliant on a child inhaling and maintaining an
open glottis during actuation of a dosimeter or during
nebulisation is unreliable. Furthermore it has been shown
in both adults [75,76] and children [77] that inspiratory
flow (which influences lung deposition) influences CRS.
Thus in children, regulation of a constant inspiratory flow
is necessary for valid results [77]. Increased CRS has been
found in children with recurrent cough [44], cough dom-
inant asthma [78] and influenza infection [79]. However
testing for CRS is non-diagnostic and its use is still limited
to research purposes. In clinical circles, the concept of a
temporal increase in CRS has been useful to explain
'expected cough'.
Use of chest and sinus CT scans
The utility of a CT scan in children has to be balanced with
the reported increased lifetime cancer mortality risk [10].
The yield of ultrafast CT scans in children with chronic
productive cough is 43%, where bronchiectasis was docu-
mented [80]. The yield of CT scan in evaluation of a dry
cough without the presence of features in table 1 is
unknown and arguably should not be performed. Lung
cancers are extremely rare in children. In children, there is
poor concordance in diagnostic modalities for diagnosing
paranasal disease [81]. Also, a single study of paranasal
sinus CT findings in children with chronic cough (>4

weeks) described that an abnormality was found in 66%
[82]. However this finding has to be interpreted in the
context of high rates (50%) of incidental sinus abnormal-
ity in asymptomatic children undergoing head CTs [83].
Abnormal sinus radiographs may be found in 18–82% of
asymptomatic children [84]. Thus, it is arguably difficult
to be confident of an objective diagnosis of nasal space
disease as the cause of cough.
Table 2: Classical recognisable cough [39,110]
Barking or brassy cough Croup [252] tracheomalacia [132,134] habit cough [157,253]
Honking Psychogenic [254]
Paroxysomal (with/without whoop) Pertussis and parapertussis [123,255]
Staccato Chlamydia in infants [256]
Cough productive of casts Plastic bronchitis [257]
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Flexible bronchoscopy
Indications for bronchoscopy in children with chronic
cough include suspicion of airway abnormality, persistent
changes on CXR, suspicion of an inhaled foreign body,
evaluation of aspiration lung disease and for microbio-
logical and lavage purposes. In these situations, cough is
usually specific rather than non-specific. Bronchoscopi-
cally defined airway abnormality was present in 46.3% of
children with chronic cough in a tertiary centre-based
study, whereas in Callahan's [85] series, bronchoscopy
assisted in diagnosis in 5.3% of children [86]. In a Euro-
pean series, chronic cough was the indication in 11.6% of
the 1233 paediatric bronchoscopies performed [87].
Spirometry

Spirometry is valuable in the diagnosis of reversible air-
way obstruction in children with chronic cough. In the
early studies on asthma presenting as chronic cough,
abnormal baseline lung function was documented
[88,89]. However spirometry is relatively insensitive
[90,91] and a normal spirometry does not exclude under-
lying respiratory abnormality. In one study of 49 children
with chronic cough, spirometry was normal in all who
were able to perform the test [86].
Tests for airway hyper-responsiveness
In adults, tests for AHR are relatively easy to perform and
direct AHR (methacholine, histamine) is used to exclude
asthma [33]. In children (outside a research setting) test-
ing for AHR is reliably performed only in older children
(>6 years) and positive AHR especially to direct AHR chal-
lenges as an indicator of asthma has questionable validity
[92,93]. Airway cellularity (sputum) in asymptomatic
children with AHR was similar to children without AHR
but significantly different to children with asthma [94]. In
children, unlike in adults, the demonstration of AHR in a
child with non-specific cough is unlikely to be helpful in
predicting the later development of asthma [95] or the
response to asthma medications [47]. The only RCT that
examined the utility of AHR and response to inhaled salb-
utamol and ICS [47] found that the presence of AHR
could not predict the efficacy of these therapies for cough
[47]. Another study showed that AHR to hypertonic saline
is significantly associated with wheeze and dyspnoea but
not associated with dry cough or nocturnal cough once
confounders were accounted for [96]. The older studies

that equated presence of AHR in children with cough as
representative of asthma were not placebo-controlled
studies, confounders were not adjusted for, or used
unconventional definitions of AHR [97-100]. A recent
study using 6 min free running test described that exercise
induced symptoms were poor predictors of bronchocon-
striction [101]. However interpretation of the study is lim-
ited [102].
Other investigatory techniques
The single study on bronchial biopsies in 7 children with
chronic cough described the association between early
ARI and epithelial inflammation [103]. Bronchial biop-
sies are easily performed in adults, but are rarely per-
formed in children except in selected centres where the
procedure has been shown to be safe [104]. Airways resist-
ance by the interrupter technique (Rint) has been used to
asses values in children with cough [105] but Rint is not
established in clinical practice and has problems with
validity of measurements when undertaken by different
investigators [106]. To date, there are no paediatric studies
that have evaluated the role of NO or breath condensate
in guiding management of chronic cough. Increased NO
has been found in asthmatics with cough [57] but is also
found in other conditions associated with cough such as
environmental pollutants [60].
Outcome measures for cough-related studies
Cough severity indices, broadly divided into subjective
and objective outcomes, measure different aspects of
cough. In children, measures of CRS have a weak relation-
ship with cough frequency. Subjective cough scores have

a stronger and consistent relationship with cough fre-
quency [107]. The choice of indices depends on the rea-
son for performing the measurement [107].
Answers to questions on isolated cough are largely poorly
reproducible [108] and nocturnal cough in children is
unreliably reported [52,53]. The kappa value relating the
chance-corrected agreement to questions on isolated
cough is poor (0.02–0.57) [19,108,109] in contrast to iso-
lated wheeze (0.7–1.0) [108]. Biased reporting of cough
has been shown; parents who smoke under-report cough
in their children [19]. Diary cards for cough have been val-
idated against an objective method and children aged >6
years are better than their parents at quantifying their
cough severity [54]. Cough-specific QOL questionnaires
exist for adults but not for children. There is a clear need
for a paediatric cough specific QOL scores, as adult QOL
scores cannot be applied to children. Cough specific
objective tests include ambulatory and non-ambulatory
objective cough meters, CRS and cough peak flows
(reviewed elsewhere) [110]. Adult type instruments
require modification for use in children [111].
Aetiological factors
Although some diseases are common to both adults and
children, the pattern of many respiratory illnesses in chil-
dren is clearly different to adults; eg viruses associated
with the common cold in adults can cause serious respira-
tory illnesses such as bronchiolitis and croup in previ-
ously well young children [112]. Both of these respiratory
syndromes are non existent in adults. Conversely, com-
mon causes of cough and respiratory diseases in adults

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such as chronic bronchitis [113] and chronic obstructive
pulmonary disease are not recognised diagnostic entities
in paediatric respiratory literature and main textbooks
[114,115]. The following highlights some of the differ-
ences between children and adults.
Cohort studies
Some hospital based clinical studies of children present-
ing with chronic cough have found asthma as the most
common cause [116,117] but others have not [43,86]. In
a prospective review of 81 children with chronic cough,
none had asthma on final diagnosis [43]. In a retrospec-
tive review of 49 children with chronic cough, none of the
children had asthma as the sole final diagnosis [86]. There
is little doubt that the aetiology of cough would depend
on the setting, selection criteria of children studied
[69,86] follow-up rate [118] and depth of clinical history,
examination and investigations performed. When airway
profiles have been examined in children with isolated
chronic cough, the studies have shown very few children
with airway inflammation consistent with asthma [68-
70]. Marguet and colleagues concluded that "chronic
cough is not associated with the cell profiles suggestive of
asthma and in isolation should not be treated with pro-
phylactic anti-asthma drugs" [70].
Acute respiratory infections and post infections
Most coughs in early childhood are caused by viral ARIs
[17,119]. In children with an ARI, 26% were still unwell
7-days after the initial consultation and 6% by day 14

[120]. Cough was however not specifically reported [120].
A systematic review on the natural history of acute cough
in children aged 0–4 years in primary care reported that
the majority of children improve with time but 5–10%
progress to develop bronchitis and/or pneumonia [17].
Post-viral cough is a term that refers to the presence of
cough after the acute viral respiratory infection. In
Monto's review [121] the mean annual incidence of total
respiratory illness per person year ranges from 5.0–7.95 in
children aged less than 4 years to 2.4–5.02 in children
aged 10–14 years [121]. A recent Australian study
recorded respiratory infection/episode rates of 2.2–5.3 per
person per year for children aged ≤10 years (mean dura-
tion of 5.5–6.8 days) [122]. That for adults (>20-years)
was 1.7 [122].
Infections such as pertussis and mycoplasma can cause
persistent cough not associated with other symptoms
[123]. Pertussis should be suspected especially if the child
has had a known contact with someone with pertussis
even if the child is fully immunised as partial vaccine fail-
ure is an emergent problem [124]. A hospital study exam-
ined PCR and serology for pertussis in a prospective
cohort of 40 children with chronic (>3 weeks) cough and
found that only 5% of these children had laboratory
evidence of pertussis [42]. No other published data on
chronic cough have examined pertussis and mycoplasma
infections with other cough etiologies. In a prospective
childhood vaccine study, presence of Chlamydia pneu-
moniae, mycoplasma, parapertussis and pertussis were
sought in children (aged 3–34 months) if a child or

household member coughed for >7 days. In total, 115
aetiological agents were identified in 64% of episodes
with cough [123]. The most common single agent was
pertussis in 56% (median cough of 51 days), followed by
Mycoplasma in 26% (cough for 23 days), Chlamydia in
17% (26 days), and parapertussis 2% [123]. Other micro-
bial studies were not done. A factor that needs to be con-
sidered when analysing such results is determining
whether the infectious agent isolated is the cause of the
cough, as the percentage of asymptomatic infection can be
very high (54%) [125]. In children who received the acel-
lular pertussis vaccination, pertussis infection is clinically
difficult to distinguish from diseases associated with
coughing caused by other viral or bacterial infections
[126].
Inhalation of foreign body
Cough is the most common symptom in some series of
acute foreign material inhalation but not in others [127].
A history of a choking episode is absent in about half
[128]. Presentations are usually acute [129] but chronic
cough can also be the presentation of previously missed
foreign body inhalation [130]. Unlike adults, a history of
acute aspiration in young children has to be obtained
from an adult who may not be present at the time of aspi-
ration. Missed foreign bodies in the airways can lead to
permanent lung damage [131].
Airway lesions and cough
Chronic cough is well described in children with airway
lesions [132-134] and at lesser frequency in adults [135].
An adult study reported that none of 24 patients with tra-

cheomalacia had chronic cough as a presenting symptom
[135]. Gormley and colleagues described that 75% of chil-
dren with tracheomalacia secondary to congenital vascu-
lar anomalies had persistent cough at presentation [134].
Other symptoms include stridor, chronic dyspnoea, recur-
rent respiratory infections and dysphagia [134]. How
common are airway lesions in asymptomatic children is
unknown and how the symptom of cough relates to air-
way lesions can only be postulated.
Environmental pulmonary toxic agents
In-utero tobacco smoke exposure alters respiratory con-
trol and responses [136,137], pulmonary development
and physiology [138,139]. Its influence on the developing
central and peripheral cough receptors, pathways and
plasticity of the cough pathway [6,140] is unknown. ETS
increases susceptibility to respiratory infections [141,142]
Cough 2005, 1:7 />Page 7 of 15
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causes adverse respiratory health outcomes [143] and
increases coughing illnesses [144,145]. Increased ETS has
also been described in cohorts of children with chronic
cough compared to children without cough
[69,69,143,144,146,147]. Indoor biomass combustion
increases coughing illness associated with acute respira-
tory infections with an exposure-response effect [148].
Exposure to other ambient pollutants (particulate matter
[149,150] nitrogen dioxide, gas cooking [151] etc) is also
associated with increased cough in children in cross sec-
tional [149,150] and longitudinal studies [152] especially
in the presence of other respiratory illnesses such as

asthma [149]. Some studies however have not shown this
effect [153,154] which is likely partially related to prob-
lems with question-based epidemiological studies on iso-
lated and nocturnal cough [14,19].
Functional respiratory disorder
Habitual cough or cough as a 'vocal tic' maybe transient or
chronic and are far more commonly reported in the pae-
diatric literature than in the adult literature [41]. In one
series, psychogenic cough accounted for 10% of children
with chronic cough [116]. A Swedish community study
described the prevalence of chronic vocal tics was 0.3% in
girls and 0.7% in boys [155]. The cough in psychogenic
cough is typically thought to be absent at night. However
objective cough recording in a child with psychogenic
cough showed that cough during sleep does occur [156].
The typical psychogenic cough (honking cough) recognis-
able in children [67,157] is rare in adults [67]. In one
study, 52% of those who had their cough recorded had
barking (brassy, croupy) or honking cough [158]. How-
ever, brassy or croupy cough is also found in other child-
hood conditions associated with cough such as
tracheomalacia [41].
The big three of chronic cough in adults
In adults, asthma, GORD, post-nasal drip (the big three)
are said to cause upto 72–90% of chronic cough
[159,160]. In contrast, there is no good data that suggest
that these are common causes of chronic cough in
children.
Asthma, reactive airway disease and cough in children
There is little doubt that children with asthma may

present with cough. However, the majority of children
with cough do not have asthma [14,69,70,161,162]. The
use of isolated cough as a marker of asthma is indeed con-
troversial with more recent evidence showing that in most
children, isolated cough does not represent asthma
[35,162]. Cough associated with asthma without a co-
existent respiratory infection is usually dry [163]. Some
medium term cohort studies on children with cough have
suggested that the majority of these children eventually
developed asthma [73,164] but other studies have not
[49,50,165,166]. The Tuscon group showed that recurrent
cough presenting early in life resolved in the majority
[166]. Furthermore, these children with recurrent cough
and without wheeze, had neither AHR nor atopy, and sig-
nificantly differed from those with classical asthma, with
or without cough [166]. Several other studies also support
McKenzie's annotation [161] which highlighted the prob-
lem of over-diagnosis of asthma based on the symptom of
cough alone [118]. In a prospective community study
with a mean follow-up period of 3 years, 56% of children
with recurrent cough aged 4–7 years later became asymp-
tomatic; 37% reported continuing cough and 7.2% devel-
oped wheeze [49]. The proportion of children in the
group who subsequently developed wheeze was similar to
the asymptomatic group, who later developed wheeze on
follow-up (10%) [49]. Faniran and colleagues concluded
in their community based study of 1178 children that
"cough variant asthma is probably a misnomer for most
children in the community who have persistent cough"
[118]. Thus in community settings, epidemiological stud-

ies have shown that isolated persistent cough is rarely
asthma [118,161,165,167]. These data have been previ-
ously reviewed [14].
Upper airways disorders and cough in children
In adults, post-nasal drip has been reported as a common
cause of cough [40]. In children, although nasal discharge
and cough have been reported as the two most prominent
symptoms in children with chronic sinusitis (30–120
days) [168] supportive evidence of cause and effect in
children is less convincing [169]. A prospective study has
shown that although sinusitis is a common condition in
childhood, it is not associated with asthma or cough when
the confounding factor of allergic rhinitis was removed
[170]. The relationship between nasal secretions and
cough is more likely linked by common aetiology (infec-
tion and/or inflammation causing both) or due to clear-
ing of secretions reaching the larynx. Using a continuous
infusion of 2.5 mls/min of distilled water into the phar-
ynx of well adults, Nishino and colleagues demonstrated
that laryngeal irritation and cough only occurred in the
presence of hypercapnia (45–55 mmHg) [171] suggesting
that pharyngeal secretions alone do not cause cough.
Physiologically this is to be expected as the pharynx is not
innervated by the vagus nerve, a necessary component of
the cough reflex [172]. One study described increased
extrathoracic AHR without bronchial AHR to metha-
choline in a group of children presenting with chronic
cough [173] and other studies have linked extrathoracic
AHR to sinusitis and rhinitis [174,175]. However, the
repeatability and validity of extrathoracic AHR in children

are ill-defined. Therapeutic approaches for allergic rhinitis
have been well summarised [176].
Cough 2005, 1:7 />Page 8 of 15
(page number not for citation purposes)
GOR and cough in children
In adults, GORD is reported to cause up to 41% of chronic
cough [177]. In non-controlled trials the improvement
rate of cough by non-surgical intervention e.g. with PPI
alone [178] or PPI with motility agents [179] for GORD
associated cough, cough improvement rates of 86–100%
have been reported [178,179]. However a systematic
review found much less convincing results [180]. In chil-
dren the data relating isolated cough to GORD is even far
less convincing. The section on upper airway symptoms of
a clinical practice guideline on the evaluation and man-
agement of children with GOR included a discussion on
cough and GOR, concluded " there is insufficient evi-
dence and experience in children for a uniform approach
to diagnosis and treatment" [181]. Cough unequivocably
(RCT setting) related to acid GOR in adults has been
reported to subside in 1–3 weeks [182] but such evidence
is unavailable in children [180] and difficult to obtain.
While GOR may be the reason for persistent cough
[183,184] cough can also cause GOR [185,186]. Proof of
cause and effect in children is rare [187] and it is difficult
to delineate cause and effect [188]. There are limited
studies which have prospectively examined causes of
chronic cough in children. Those available suggest GOR is
infrequently the sole cause of isolated cough in children.
One prospective study of the causes of chronic cough in

children found only one child with GOR out of a series of
38 [116]. A retrospective study found co-existent GOR in
4 of 49 children with chronic cough [86]. In contrast to
data in adults where GOR is a frequent cause of chronic
cough [159,189] there is indeed no current convincing
evidence that GOR is a common cause of non-specific
cough in children. Although case series have shown the
link between supra-oesophageal reflux and GOR in chil-
dren, there is a lack of convincing data, as Rudolph sum-
marised "No studies have definitively demonstrated
symptom improvement with medical or surgical therapy
for the latter symptom presentations" [190].
Other aetiologies
Eosinophilic bronchitis and allergy
Eosinophilic bronchitis, a well described cause of chronic
cough in adults [191] is not well recognised in children.
'Allergic or atopic cough' is a poorly defined condition
even in adults [192]. The association between atopy and
respiratory symptoms has been the subject of many epide-
miological studies [193,194]. Some have described
greater respiratory symptom chronicity [195] but others
have not [193,194]. Inconsistent findings regarding
cough and atopy are also present in the literature; reports
of increased atopy (or diseases associated with atopy) in
children with cough have been found in some cohort and
cross sectional studies [165,196] but not in others
[46,47,56,166]. Cough as a functional symptom can also
be mistaken for an allergic disorder in children [197].
Medications and treatment side-effects
Chronic cough has been reported as a side effect of ACE

inhibitors (2–16.7%) [198-200], inhaled ICS [201] and as
a complication of chronic vagus nerve stimulation [202].
In children, cough associated with ACE inhibitors resolves
within days (3–7 days) after withdrawing the medication
[198,199] and may not recur when the medication is
recommenced [199]. The package insert for omeprazole
includes cough as an adverse event in 1.1% of adults and
a single case report was recently published [203] but no
reports on children were found.
Otogenic causes – Arnold's ear-cough reflex
In approximately 2.3–4.2% of people (bilateral in 0.3–
2%), the auricular branch of the vagus nerve is present
and the Arnold's ear-cough reflex can be elicited [204-
206]. Case reports of chronic cough associated with ear
canal stimulation from wax impaction and cholesteatoma
have been reported [207,208]. In children, the signifi-
cance of the ear reflex and cough was described as early as
1963 [209] although recently reported again [210].
Management options of non-specific cough
Cough is subject to the period-effect (spontaneous resolu-
tion of cough) [211] and thus non-placebo controlled
intervention studies have to be interpreted with caution
[212]. If any medications are trialled, a 'time to response'
should be considered and considerations given to patient
profile and setting (eg community practice vs tertiary hos-
pital practice). The same empirical therapy (for asthma,
GOR, and PND) suggested in adults [33] is largely inap-
propriate in children.
Physician and parental expectations
Providing parents with information on the expected time

length of resolution of acute respiratory infections may
reduce anxiety in parents and the need for medication use
and additional consultation [120]. Appreciation of spe-
cific concerns and anxieties, and an understanding of why
they present are thus important when consulting children
with non-specific cough. Educational input is best done
with consultation about the child's specific condition
[213]. A RCT [214] examining the effect of a pamphlet
and a videotape promoting the judicious use of antibiot-
ics, found that their simple educational effort was success-
ful in modifying parental attitudes about the judicious use
of antibiotics.
Over the counter cough medications and anti-histamines
In contrast to adults where OTC medications, in particular
codeine and its derivatives have been shown to be useful,
systemic reviews for children have concluded that cough
OTCs have little, if any, benefit in the symptomatic con-
trol of cough in children [215,216]. Moreover OTCs have
significant morbidity and mortality [217,218] and are
Cough 2005, 1:7 />Page 9 of 15
(page number not for citation purposes)
common unintentional ingestions in children aged <5
years [219]. Use of diphenhydramine is also non benefi-
cial for symptomatic treatment of cough related to pertus-
sis [220]. The use of steam inhalation, vitamin C, zinc,
and echinacea for upper RTI has been summarised [221]
with little benefit, if any, for symptomatic relief of cough
for adults and children.
The efficacy of anti-histamines in relieving cough in chil-
dren is minimal, if at all [222]. Thus, unlike adults, the use

of anti-histamine therapy for chronic cough in children is
mostly unjustified. Whether this difference between chil-
dren and adults is related to atopic states is unknown. A
RCT on ketotifen did not show any clinical benefit in the
treatment of 113 infants and children with chronic cough
and/or wheeze [223]. A systematic review of anti-hista-
mine and nasal decongestion combinations, and anti-his-
tamines in OTC medications has shown that these
pharmaceuticals were no more likely than placebo in
reducing acute cough in children [215]. The use of these
medications that contain H
1
receptor antagonist has to be
balanced with adverse events [217,224,225] which
includes reported death from toxicity in young children
[217,218]. The latest published RCT (n = 100) also
showed that diphenhydramine (a first generation H
1
-
antagonist) and dextromethorphan were no different to
placebo in reducing nocturnal cough or sleep disturbance
in both the children and parent(s) [225]. Like other RCTs
there was a significant improvement in both placebo and
active arms for the cough outcomes measured [225].
Asthma therapy for cough
Old cohort studies describing that asthma therapy for that
era (oral orciprenaline, salbutamol syrup [226,227] theo-
phylline [97,227] and metaproterenol with theophylline)
[88] was useful in abolishing cough included children
with clinically recognisable asthma. For example, 8 of 11

children in Konig's study had cough with co-existant chest
pain or dyspnea on exertion) [88] 10 of 32 children in
another study had abnormal examination findings [89].
In ambulatory children with acute cough (1–10 days)
with no history of asthma and a normal chest examina-
tion, oral albuterol was not effective in reducing cough
frequency or duration [48]. In a meta-analysis, Smucy et
al likewise concluded that "there is no evidence to support
using beta2-agonists in children with acute cough and no
evidence of airflow obstruction" [228]. There is only one
study on use of inhaled salbutamol in chronic cough
(median of 8-weeks) which also showed no benefit [47].
There is no evidence for the use of anti-cholinergics for in
children with non-specific cough [229]. Use of bron-
chodilators must be weighed against adverse events (eg
tremor, irritability [48] behaviour change, cost).
Only 2 RCTs on ICS for chronic non-specific cough in
children have been published and both groups have cau-
tioned against prolonged use of ICS [46,47]. There is no
RCT on oral steroids for non-specific cough in children. In
cough associated with pertussis, dexamethasone provides
no significant benefit for the symptomatic relief of cough
[220]. Even in children with wheeze, a RCT found that
oral steroids may confer no benefit [230]. In contrast to
high doses used in adults, low dose ICS has been shown
to be effective in the management of the majority of child-
hood asthma [231-233] and there were reported signifi-
cant adverse events on high doses [234,235]. Thus if a trial
of asthma therapy is ever warranted, use of a moderate
dose (400 mcg/day equivalent of budesonide) is sug-

gested. This practice is however discouraged in most set-
tings. As the earlier studies in adults and children that
utilised medications for asthma for the era reported that
cough related to asthma completely resolved by 2–7 days
[88,89,97,236] it is recommended that reassessment is
done in 2–3 weeks. Cough unresponsive to ICS should
not be treated with increased doses of ICS. Cough that
resolves with ICS use may be related to the period effect
(spontaneous resolution) [211] or a transient effect
responsive to ICS use (ICS may also impact on non-asth-
matic airways with pulmonary toxicants [237]). Thus cli-
nicians should be cognisant that the child that appears to
respond to ICS does not necessarily have asthma and the
child should be re-evaluated off asthma treatment.
Cromoglycate and nedocromil reduces cough associated
with asthma [238,239] and in children born prematurely
[240]. An open, single arm trial reported significant reduc-
tion in cough scores from 30 to 15/week after 2-weeks of
treatment with nedocromil (4 mg qid) with no additional
benefit in subsequent 4-weeks [241]. There are no pub-
lished RCTs [242]. Leukotriene receptor antagonists have
been examined in adults for cough [243] but there is no
RCT data in children. Theophylline utilized in old studies
[97,227] may have an effect on cough separate from its
'anti-asthmatic' properties but there are no RCTs in chil-
dren [244] and theophylline has a narrow therapeutic
range. Oral theophylline, but not placebo, induced com-
plete remission in adults with ACE inhibitor related cough
[245]. There is a need for RCTs examining the effective-
ness of theophylline for non-specific cough in children.

Anti-microbials
The American Academy of Family Physician's guidelines
discourages use of antibiotics except when rhinosinusitis
and cough are present and not improving after 10 days
[246]. Meta-analysis on anti-microbials for acute bronchi-
tis (recent onset of productive cough without chronic
obstructive pulmonary disease, sinusitis or pneumonia)
in older children (aged >8 years) and adults showed a
small benefit of 0.58 days but with significantly more
Cough 2005, 1:7 />Page 10 of 15
(page number not for citation purposes)
adverse events [221]. In subacute cough, two paediatric
RCT have shown that anti-microbials (amoxycillin/clavu-
lanic acid [247] and erythromycin [248]) were more likely
to achieve 'clinical cure' and also prevented progression of
illness defined by need for antibiotics [249]. The quality
of cough in both studies was not clearly defined but the
secretions in both studies cultured M catarrhalis
[247,248].
Cessation of ETS and other environmental toxicants
In the management of any child with cough irrespective of
the aetiology, attention to exacerbation factors is encour-
aged. A single report was found on cessation of parental
smoking as a successful form of therapy for the children's
cough [250]. Behavioural counselling for smoking moth-
ers has been shown to reduce young children's ETS expo-
sure in both reported and objective measures of ETS
[251].
Conclusion
Cough is very common and in the majority is reflective of

expected childhood respiratory infections. However
cough may also be representative of a significant serious
disorder and all children with chronic cough should have
a thorough clinical review to identify specific respiratory
pointers. Physiologically, there are similarities and signif-
icant differences between adults and children. Expectedly,
the aetiologies and management of cough in a child differ
to those in an adult. Cough in children should be treated
based on aetiology and there is no evidence for using
medications for symptomatic relief of cough or for an
empirical approach based on the big three adult aetiolo-
gies. The use of medications are discouraged based on cur-
rent evidence and if medications are used, it is imperative
that the children are reviewed within the time frame of
'time to response' and medications ceased if there is no
effect. Irrespective of diagnosis, environmental influences
and parental expectations should be reviewed and man-
aged accordingly as cough impacts on the quality of life of
parents and children. Children with cough should be
managed differently to adults as the aetiological factors
and treatment in children differ to those in adults.
Abbreviations
ACE Angiotensin converting enzyme
AHR Airway hyper-responsiveness
ARI Acute respiratory infection
CRS Cough receptor sensitivity
CXR Chest X-Ray
CT Computed Tomography
ETS Exposure to tobacco smoke
FTT Failure to thrive

GOR Gastroesophageal reflux
HRCT High resolution computed tomography of the chest
ICS Inhaled corticosteroids
OTC Over the counter
eNO exhaled nitric oxide
QOL Quality of Life
RCT Randomised controlled trial
PCR Polymerase chain reaction
Competing interests
No actual or potential conflict of interest exists.
AB Chang is funded by the Australian National Health
Medical Research Council and the Royal Children's Hos-
pital Foundation
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